The impact of wound infections on our healthcare system is enormous. Infections of the dermis, including burns, surgical-site infections and non-healing diabetic foot ulcers affect over a million people, cause thousands of amputations and deaths and cost billions of dollars in direct medical costs in the United States annually. The microbial populations of these infections are typically polymicrobial, biofilm- associated, and display increased tolerance to antimicrobials, but despite the prevalence and severity of wound infections, microbial interactions in this environment have been significantly understudied. We hypothesize that the wound environment promotes co-infection with Pseudomonas aeruginosa and Staphylococcus aureus, resulting in chronic wound infections that are extremely tolerant to antimicrobials. Our goals are to 1) characterize P. aeruginosa and S. aureus interspecies interactions in an in vitro wound environment; 2) determine how components of the wound environment inhibit P. aeruginosa's ability to kill S. aureus and thus promote stable coinfections; and 3) investigate what consequences P. aeruginosa/S. aureus coinfection has on wound resolution in vivo. To complete these goals we will use an innovative in vitro wound model to study the population dynamics of P. aeruginosa/S. aureus coinfection in response to environmental stimuli, and a mouse chronic wound model to test whether coinfection results in wounds that more difficult to treat or slower to heal. The results of this project will provide important new information about how the interspecies relationship of these two extremely important and prevalent wound pathogens influences wound infections.